U.S. patent number 4,684,517 [Application Number 06/913,584] was granted by the patent office on 1987-08-04 for mouthrinse composition containing hydrogen peroxide and fluoride.
This patent grant is currently assigned to Colgate-Palmolive Company. Invention is credited to Donald Clipper, James Norfleet.
United States Patent |
4,684,517 |
Clipper , et al. |
August 4, 1987 |
Mouthrinse composition containing hydrogen peroxide and
fluoride
Abstract
An aqueous storage-stable mouthwash composition, optionally in
the form of a gel and optionally containing special wintergreen or
cinnamon flavor mixtures, comprising about 0.5 to about 5% by
weight of hydrogen peroxide and about 0.01 to about 2% by weight of
a compound providing fluoride or fluoride-containing ions in the
composition.
Inventors: |
Clipper; Donald (Belle Mead,
NJ), Norfleet; James (Plainfield, NJ) |
Assignee: |
Colgate-Palmolive Company (New
York, NY)
|
Family
ID: |
27106048 |
Appl.
No.: |
06/913,584 |
Filed: |
September 30, 1986 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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697614 |
Feb 4, 1985 |
|
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|
579835 |
Feb 13, 1984 |
4537778 |
|
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455388 |
Jan 3, 1983 |
4431631 |
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Current U.S.
Class: |
424/52; 424/53;
424/673 |
Current CPC
Class: |
A61K
8/042 (20130101); A61K 8/21 (20130101); A61K
8/22 (20130101); A61Q 11/00 (20130101); A61K
8/34 (20130101); A61K 8/37 (20130101); A61K
8/922 (20130101); A61K 8/33 (20130101) |
Current International
Class: |
A61K
33/16 (20060101); A61K 007/18 (); A61K 007/20 ();
A61K 033/16 () |
Field of
Search: |
;424/52,53,151 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Rose; Shep K.
Attorney, Agent or Firm: Sylvester; Herbert S. Grill; Murray
M. Blumenkopf; Norman
Parent Case Text
This application is a continuation of application Ser. No. 697,614
filed Feb. 4, 1985 and now abandoned, which was a
continuation-in-part of application Ser. No. 597,835 filed Feb. 13,
1984 and now U.S. Pat. No. 4,537,778, which was in turn a
continuation-in-part of application Ser. No. 455,388 filed Jan. 3,
1983 and now U.S. Pat. No. 4,431,631.
Claims
We claim:
1. An aqueous storage-stable mouthwash composition comprising: from
about 0.5 to about 5% by weight of hydrogen peroxide, and from
about 0.01 to about 2% by weight of a compound providing fluoride
or fluoride-containing ions in the aqueous composition.
2. A mouthwash composition according to claim 1 further including
from about 3 to 10% by weight of ethanol.
3. A mouthwash composition according to claim 1 further including
from about 1 to 20% by weight of polyhydric alcohol.
4. A mouthwash composition according to claim 1 further including
from about 0.1% to about 10% non-ionic surfactant.
5. A mouthwash composition according to claim 1 wherein the amount
of hydrogen peroxide is from about 1% to about 3%, and further
including about 0.5 to 5% non-ionic surfactant, about 3-10% ethanol
and about 3-15% polyhydric alcohol selected from glycerol and
sorbitol.
6. A mouthwash composition according to claim 5 wherein the
nonionic surfactant comprises from about 0.5% to 3% of a water
soluble polyoxyethylenated-polyoxypropylene polyol and from about
0.3% to 2% of a water soluble polyoxyethylenated monoester of
sorbitol with a C.sub.10 to C.sub.18 fatty acid.
7. An aqueous oral gel comprising the mouthwash composition of
claim 1.
8. An aqueous oral gel according to calim 7 including from about 1%
to about 50% of a gelling agent.
9. An aqueous oral gel according to claim 8 wherein the amount of
gelling agent is from about 5% to 30% by weight of the gel.
10. An aqueous oral gel according to claim 9 wherein the gelling
agent is a water-soluble polyoxyethylenated polyoxypropylene
polyol.
11. An aqueous oral gel according to claim 10 wherein the gelling
agent contains a polyoxypropylene hydrophobe of about 3,500-4,000
M.W. and about 30 to 80% of hydrophilic polyoxyethylene groups.
12. A mouthwash composition according to claim 1 further including
a flavoring agent selected from the group consisting of:
(1) wintergreen flavor containing methyl salicylate and menthol in
a weight ratio of about 3:1 to 5:1, and
(2) cinnamon flavor containing 6-9% menthol, 32-38% cinnamic
aldehyde and 6-9% clove oil.
13. A mouthwash composition according to claim 1 including a
coloring agent.
14. A method comprising rinsing the oral cavity with the mouthwash
composition of claim 1.
15. A method comprising rinsing the oral cavity with the mouthwash
composition of claim 5.
16. A method comprising rinsing the oral cavity with the mouthwash
composition of claim 6.
17. A method comprising selectively treating areas of the oral
cavity with the aqueous oral gel of claim 7.
18. A method comprising selectively treating areas of the oral
cavity with the aqueous oral gel of claim 8.
19. A method comprising selectively treating areas of the oral
cavity with the aqueous oral gel of claim 10.
Description
This invention relates to an oral preparation and especially to an
aqueous peroxide mouthwash or mouthrinse solution, gel or paste,
containing a fluoride.
It has long been recognized in the art that hydrogen peroxide and
other peroxygen-containing agents are effective in curative and/or
prophylatic treatments with respect to caries, dental plaque,
gingivitis, periodontitis, mouth odor, tooth stains, recurrent
aphthous ulcers, denture irritations, orthodontic appliance
lesions, postextraction and postperiodontal surgery, traumatic oral
lesions and mucosal infections, herpetic stomatitis and the like.
Peroxide-containing agents in the oral cavity exert a
chemomechanical action generating thousands of tiny oxygen bubbles
produced by interaction with tissue and salivary enzymes. The
swishing action of a mouthrinse enhances this inherent
chemomechanical action. Such action has been recommended for
delivery of other agents into infected gingival crevices. Peroxide
mouthrinses and other oral preparations prevent colonization and
multiplication of anaerobic bacteria known to be associated with
periodontal disease. Peroxygen-containing gels or pastes are
indicated and/or desirable where it is required to selectively
treat areas for more than a few seconds, such gels and pastes
tending to remain at the site of application for a time sufficient
for the peroxide to manifest its maximum effectiveness.
It is however also known that most peroxy compounds such as
hydrogen peroxide and metal peroxides such as magnesium peroxide in
such oral compositions, by interaction with other common excipients
therein, tend to be unstable in storage, continuously losing the
capacity to release active or nascent oxygen over relatively short
periods of time, and tend to diminish or destroy the desired
function of such excipients. Among such excipients are flavors and
coloring agents added to enhance the acceptability of the
preparations to those in need of an oral peroxidizing treatment.
Numerous proposals have been made for solving the aforementioned
problems, including encapsulating the peroxide compound and/or the
peroxide-sensitive excipients, using more stable but more expensive
peroxy compounds such as organic peroxides and peroxydiphosphate
salts (e.g. the tetrapotassium salt), etc. In addition such
flavored and/or colored peroxide products exhibit a gradual
decrease in pH of from about 1 to 3 pH units.
It is an object of this invention to provide oral preparation which
will not be subject to one or more of the aforementioned
disadavantages and deficiencies. Another object of this invention
is the provision of a foaming oxygenating oral preparation in
ready-to-use form having a pleasant flavor and/or color and
enhanced stability in storage. Still another object of this
invention is the provision of a mouthrinse having a basis of the
readily available, highly effective and economical hydrogen
peroxide. Still a further object of this invention is provision of
an oxygenating oral preparation containing an anti-caries agent
such as fluoride. Yet a further object of this invention is the
provision of an oral oxygenating preparation in the form of a gel,
also with an anti-caries agent e.g. fluoride. Other objects and
advantages will appear as the description proceeds.
The attainment of one or more of the above objects is made possible
by this invention which comprises:
an aqueous oral preparation containing, approximately by weight:
from about 0.5 to about 5% by weight of hydrogen peroxide and from
about 0.01 to about 2% by weight of a compound providing fluoride
or fluoride-containing ions in the aqueous composition, and
preferably also containing an effective flavoring amount of a
flavor selected from the group consisting of
(1) wintergreen flavor containing methyl salicylate and menthol in
a weight ratio of about 3:1 to 5:1, and
(2) a cinnamon flavor composition comprising about 6-9% menthol,
32-38% cinnamic aldehyde and 6-9% clove oil.
The aforementioned component "B" flavors have surprisingly been
found to be satisfactorily stable and compatible in the presence of
hydrogen peroxide, in contrast to other flavors, e.g. fruity
flavors such as orange, lemon and lime, and even minty flavors
other than the aforesaid b1 component wintergreen flavor, such as
peppermint and spearmint. Effective flavor amounts are as desired,
typically ranging from about 0.05 to 1.0%, preferably about 0.1 to
0.5%, by weight of the oral composition.
It is generally desirable, and often preferred to include numerous
adjuvants to the basic compositions of this invention. These
include (C) ethanol; (D) polyhydric alcohols such as glycerol and
sorbitol; (E) surfactants, especially nonionics, and of these,
those which have been found to have acceptable stability in the
aqueous peroxygen environment; (F) a sweetener; (G) anti-caries
agents; (H) thickeners; (I) preservatives; (J) coloring agents; and
the like.
With reference to the ethyl alcohol a convenient amount is 1 to 5%
by weight based on the weight of the total composition, with 3-10%
being a preferred range. The polyhydric alcohol (D) may range from
about 1 to 20% by weight, with 3-15% being preferred.
Sorbitol is preferred as the component D polyhydric alcohol since
although glycerin is sufficiently compatible with the other
components, particularly the hydrogen peroxide, it interferes with
at least one common method for analysis of the peroxide content.
Component D serves hymectant, carrier (with the ethanol) and
viscosity-control agent.
The component E surfactant, which is preferably nonionic comprises,
in the more preferred embodiments, two general types of
surfactants; those known under the Tween and other trademarks and
those block polymers available under the Pluronic trademarks. The
former (Tween) surfactants are mixtures of C.sub.10-18 fatty acid
esters of sorbitol (and sorbitol anhydrides), consisting
predominantly of the monester, condensed with about 10-30,
preferably about 20, moles of ethyleneoxide. The fatty acid
(aliphatic hydrocarbyl monocarboxylic acid) may be saturated or
unsaturated, e.g. lauric, palmitic, stearic, oleic acids.
Polysorbate 20 (e.g. Tween 20) is especially preferred, commonly
referred to as polyoxyethylene (20) sorbitan monolaurate. The
Pluronic surfactants are straight chain polymers containing a
hydrophobic (water insoluble) polyoxypropylene moiety
polyoxyethylenated at both ends with sufficient water-solubilizing
oxyethylene groups to achieve the desired water-solubility, HLB,
(hydrophyliclipophylic balance) and dispersing surfactant activity.
The solid F series of Pluronics are preferred in which the
molecular weight of the polyoxypropylene moiety ranges from about
950 to 4,000 and constitutes about 20-30% of the molecule (i.e.
80-70% polyoxyethylene in the molecule). Pluronic F 108 is
especially preferred, in which the said hydrophobic moiety has a
molecular weight of about 3250 and constitutes about 2% of the
molecule. This surfactant has a molecular weight of about
14,000-16,000.
The surfactant components serve as solubilizing, dispersing,
emulsifying, wetting and viscosity-control agents and when used in
certain combinations, are especially effective to solubilize the
flavor.
A particularly useful combination of surfactants is one where at
least one surfactant is of the Pluronic type and at least one is of
the polysorbate type.
For the aforementioned functions of solubilizing, dispersing,
emulsifying, wetting and viscosity-control, it is preferred to use
from about 0.1% to about 10% by weight of surfactant; more
preferred range is about 0.2% to about 6% and a most preferred
range is from about 0.5 to about 5%.
Where combination of Pluronic and Polysorbate surfactants are used
they may be employed in weight ratios of from about 20:1 to about
1:10 and preferably from about 10:1 to about 1:5.
As described above the compositions of this invention may contain
other functional agents such as anticaries agents and the like.
Fluorine-providing anticaries compounds optionally present in these
solutions may be partially or fully water-soluble. They are
characterized by their ability to release fluorine-containing ions
in water and by substantial freedom from reaction with other
compounds of the oral preparation. Among these materials are
inorganic fluoride salts such as ammonium fluoride, calcium
fluoride, a copper fluoride such as cuprous fluoride, zinc
fluoride, a tin fluoride such as stannic fluoride or stannous
chlorofluoride, barium fluoride, sodium fluorosilicate, ammonium
fluorosilicate, sodium fluorozirconate, sodium monofluorophosphate,
aluminum mono- and di-fluorophosphate, and fluorinated sodium
calcium pyrophosphate. Alkali metal and tin fluorides, such as
sodium and stannous fluorides, sodium monofluorophosphate (MFP) and
mixtures thereof, are preferred.
The amount of the fluorine-providing compound is dependent to some
extent upon the type of compound, its solubility, and the type of
oral preparation, but it must be a nontoxic amount. An amount of
such compound which releases a maximum of about 1% of fluoride ion
by weight of the preparation is considered satisfactory. Any
suitable mininum amount of such compound may be used, but it is
preferable to employ sufficient compound to release about 0.005 to
1%, and preferably about 0.1% of fluoride ion. Typically,
especially in the cases of MFP, alkali metal fluorides and stannous
fluoride, this component is optionally present in these
compositions in an amount of about 0.01 to 2 wt. %, preferably
about 0.05 to 1 wt. %, especially about 0.76 wt. %.
It has been found that in peroxygen compound-containing
compositions, and particularly in aqueous hydrogen peroxide, the pH
equilibriates generally 1 to 3 pH units below the initial pH of the
composition as it is prepared. This equilibrium value may occur
from several months to a matter of a year or more later and it
occurs in a sealed environment (i.e. not exposed to the
atmosphere), as further described below. In the fluoride-containing
composition of this invention it has been found that the
equilibrium pH is much closer to the initially prepared pH with the
maximum decrease being less than 0.5 pH units and the equilibrium
value somewhat less than that. It is quite surprising that the
presence of a fluoride, such as sodium fluoride, which is a neutral
salt should have this pH stabilizing effect on aqueous peroxygen
systems.
A coloring agent is also often desirable for enhanced appearance
and acceptability, but should be carefully selected for
compatibility with the other named components, particularly the
hydrogen peroxide. Green coloring agents for example have been
generally found to be unacceptable in this regard. FD & C Blue
No. 1 and Red No. 40 have been found to satisfy the requirements of
this invention, employed in effective coloring amounts as desired,
typically in concentrations of about 0.0002 to 0.004% by weight in
the solution.
A preferred component F sweetener compound is saccharin, especially
sodium saccharin, but other known orally acceptable sweetener
compounds may be employed, typically in concentrations of about
0.01 to 5 wt.%, such as xylitol, sodium cyclamate, perillartine,
D-tryptophan, aspartame, dihydrochalcones and the like.
One preferred form of the oral compositions of this invention is as
a solution in an aqueous and preferably an aqueousethyl alcohol
carrier. A typical mode of preparation involves judiciously mixing
the selected components for proper solubilization in the carrier
medium (e.g. ethanol/polyhydric alcohol/water), any coloring agent
and hydrogen peroxide in order being preferably added after any of
the other selected components.
As pointed out above one may incorporate into the oral compositions
of this invention any of the conventional preservatives (e.g. in
weight amounts up to about 5% and preferably about 0.01% to about
1%) which are pharmaceutically acceptable.
Further one may formulate the compositions as gels or pastes
utilizing, preferably peroxide-stable thickening and gelling
agents. Useable agents include xanthan gum, guar gum, locust gum,
carboxylic interpolymers as disclosed in U.S. Pat. No. 2,798,053, a
water soluble carboxymethyl cellulose such as sodium carboxymethyl
cellulose, and Pluronic Polyols particularly of the "10" and "12"
Series and of these especially the solid products with a hydrophobe
of M.W. of about 3500 to 4000 and with from 30 to 80% hydrophilic
polyoxyethylene groups. Examples of such Pluronic compounds are
P103, P104, P105, P123 F108 and F127. The most preferred gelling
agent is Pluronic F127. The amount of thickener or gelling agent
may vary widely. As little as 1 or 2 or 3 or 4 or 5% may suffice
for some applications whereas for most gels a most representative
range would be 5 to 50% with 10 to 30 preferred and 15 to 25 most
preferred.
The pH of the solutions and other pastes and gels of this invention
generally ranges from about 4 to 7, and preferably about 5.
Generally, the pH may be from 6 to 7 when the composition is first
prepared and then slowly drop to an equilibrium pH of from about 4
to about 6.
The following examples of preferred embodiments of this invention
are only illustrative. All amounts and proportions referred to
herein and in the appended claims are by weight unless otherwise
indicated. Typically, in preparing these exemplified formulations,
the flavor is first added to the carrier liquid, e.g. ethanol, with
agitation. The component E surfactants where used, are then slowly
sprinkled in with constant stirring for about ten minutes or until
all the surfactants are dissolved and the solution is clear. The
component D polyhydric alcohol, if used, is then added slowly with
stirring followed by addition of the optional component F
sweetener, preferably previously solubilized in a little water.
Coloring agent, hydrogen peroxide (in the form of a 35% aqueous
solution), and the remainder of the water are then added in
succession.
The pastes and gels may be prepared from the formulation liquids
merely by adding the thickener and/or gelling agent and if
necessary the peroxygen source to bring it up to specifications in
the final formula. Alternatively, all of the ingredients are added
as above for solution preparation except before adding the
peroxide, the gelling agent and/or thickener in aliquot portion of
water is added followed by the peroxide. In this procedure one may
also add the flavors after the thickener rather than at the
onset.
TABLE 1 ______________________________________ Examples (% w/v) 1 2
3 4 5 6 ______________________________________ Ethanol.sup.1 4.75
4.75 4.75 4.75 4.75 4.75 Wintergreen Flavor.sup.2 0.22 0.22 0.22
0.22 Cinnamon Flavor.sup.3 0.15 0.15 Pluronic F108 1.0 1.0 1.0 1.0
1.0 1.0 Polysorbate 20.sup.4 0.6 0.6 0.6 0.6 0.6 0.6 Sorbitol.sup.5
10.5 10.5 10.5 Glycerin 5.0 5.0 5.0 Sodium saccharin 0.04 0.04 0.04
0.04 0.04 0.04 FD & C Blue No. 1.sup.6 .0004 .0004 FD & C
Red No. 40.sup.6 .002 .002 Hydrogen peroxide.sup.7 1.5 1.5 1.5 1.5
1.5 1.5 Purified Water .rarw. q.s. to 100 v. .fwdarw. (USP
Deionized) ______________________________________ .sup.1 in form of
95% soln .sup.2 80% methyl salicylate, 20% menthol .sup.3 7.5%
menthol, 35% cinnamic aldehyde, 7.5% clove oil in propylene glycol
soln .sup.4 Tween 20polyoxyethylene (20) sorbitan monolaurate
.sup.5 in form of 70% soln .sup.6 in form of 1% soln .sup.7 in form
of 35% soln
All the above-exemplified formulations represent satisfactory,
pleasing, acceptable and effective foaming oxygenating mouthrinses
having satisfactory storage stability with respect to flavor,
color, appearance, taste, peroxy content and the like.
The foregoing examples are repeated except 18% of Pluronic F127
gelling agent is provided in formulations and in each instance
good, "ringing" gel is produced. The gelling agent is mixed with a
major amount (90%) of the formula water and polyhydride alcohol to
which is added the alcohol, flavor and surfactant (F108 and
polysorbate) mixture and finally the saccharin, colorant (s) and
hydrogen peroxide. The temperature is generally maintained at
around 0.degree. C. (e.g. -5.degree. to 10.degree. C.) during
preparation of water gelling agent mixture and also during addition
of other ingredient to this mixture. These examples are 1a to
6a.
EXAMPLE 7
75 grams of a 70% aqueous solution of sorbitol, 2.0 mg. of Blue Dye
#1 and 470 ml of water are mixed and cooled to 5.degree. C. To the
mixture first there is added 125 grams of Pluronic F127 and after
dissolution thereof there are added 1.1 grams of Wintergreen Flavor
(as in Examples 1-6) and 21.4 grams of 35% aqueous hydrogen
peroxide (USP). The mixture is allowed to come to room temperature.
The next day it is noted that a good gel has formed. The amount of
gelling agent (i.e. Pluronic F127) is about 18% by weight.
EXAMPLE 8
Example 7 is repeated except that along with initial mixture of
sorbitol, dye and water there is added 5 grams of Carbopol 934 (a
carboxylated vinyl polymer). The resultant product after a few days
is a "heavy syrup".
EXAMPLE 9
25 grams of 95% USP ethanol and 0.85 grams of Wintergreen flavor
(0.68 g. methyl salicylate and 0.17 g. USP menthol) are mixed. To
this is added 3.85 g. of Pluronic F108 and mixing is done for 20
minutes. Then 1.25 g. of water are added with mixing. 2.3 g. of
Polysorbate 20 N.F. (non-ionic) is added and mixed for 10 minutes.
To 2.85 g. of water are added 60 g. of 70% aqueous sorbitol (USP)
and the temperature lowered to 0.degree.-5.degree. C. To this cold
solution are added 100 g. of Pluronic F127. It is noted that
temperature drops to -2.degree. C. Mixing is done for 40 minutes.
To this cold mixture is added the alcohol, flavor, Pluronic F108,
and Polysorbate mixture. Then 0.15 g. of sodium saccharin (USP),
0.0015 g. FD & C Blue #1, and 21.43 g. of 35% aqueous hydrogen
peroxide are added and well mixed for about 10 minutes. Excellent
gel is formed.
EXAMPLE 10
A fluoride-containing mouthrinse of the following composition is
prepared following the typical procedure hereinbefore
mentioned:
______________________________________ Alcohol USP 95% 200.0 gm
Flavor (as in Ex. 1) 4.0 gm Pluronic F-108 40.0 gm Sorbitol USP
(70% aqueous solution) 600.0 gm Sodium Saccharin USP 1.6 gm FD
& C Blue No. 1 (1% solution) 2.8 gm Hydrogen peroxide (35%)
171.43 gm Polysorbate 20 (as in Ex. 1) 24.0 gm Sodium Fluoride USP
1.94 gm Purified Water USP as to 4000 cc
______________________________________
As prepared the pH of the formulations is 5.11. After almost 4
months the pH has dropped to only 4.91 and after 10 months it is
4.72. At equilibrium (several months later) the pH is 4.75. In a
similar batch but without the sodium fluoride, the pH which
initially is 5.10, drops to 3.69 after 10 months and several months
thereafter it has dropped a bit further to 3.65.
Similar results occur in systems without the flavor & color in
one case and without the surfactants and/or saccharin in another
case. The presence or absence of the alcohol does not affect the
results.
This invention has been disclosed with respect to preferred
embodiments, and various modifications and variations thereof
obvious to those skilled in the art are to be included within the
spirit and purview of this application and the scope of the
appended claims.
* * * * *